Enzymeless DNA Base Identification by Chemical Stepping in a Nanopore

• Published in: Journal of the American Chemical Society Vol. 143; no. 43; pp. 18181 - 18187
• Main Authors: Qing, Yujia, Bayley, Hagan
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 03.11.2021
• Subjects: Base Sequence; biopolymers; DNA; DNA - analysis; DNA - chemistry; drug therapy; Electrochemical Techniques - methods; guanine; Hemolysin Proteins - chemistry; Nanopores; platinum; polypeptides; polysaccharides; RNA; Sequence Analysis, DNA - methods
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.1c07497

The stepwise movement of a single biopolymer strand through a nanoscopic detector for the sequential identification of its building blocks offers a universal means for single-molecule sequencing. This principle has been implemented in portable sequencers that use enzymes to move DNA or RNA through hundreds of individual nanopore detectors positioned in an array. Nevertheless, its application to the sequencing of other biopolymers, including polypeptides and polysaccharides, has not progressed because suitable enzymes are lacking. Recently, we devised a purely chemical means to move molecules processively in steps comparable to the repeat distances in biopolymers. Here, with this chemical approach, we demonstrate sequential nucleobase identification during DNA translocation through a nanopore. Further, the relative location of a guanine modification with a chemotherapeutic platinum derivative is pinpointed with single-base resolution. After further development, chemical translocation might replace stepping by enzymes for highly parallel single-molecule biopolymer sequencing.